反应详情

To a solution of methyl 3-chloro-5-(methylsulfonyl)benzoate (1.32 g, 5.31 mmol) in THF (15 mL) were added PEPPSI-IPr (72.1 mg, 106 μmol, CAS RN 905459-27-0), cyclopropylzinc(II) bromide (0.5 M solution in THF, 25.5 mL, 12.7 mmol) and 1,3-dimethyl-2-imidazolidinone (3 mL) and the reaction mixture was heated to reflux for 22 hours before another batch of cyclopropylzinc(II) bromide (0.5 M solution in THF, 12.7 mL, 6.37 mmol) was added. Stirring at reflux was continued for 22 hours. The reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were washed once with saturated aqueous NaHCO3 solution. The pH of the aqueous phase was adjusted to 1, saturated with solid sodium chloride and extracted three times with EtOAc. The organic layers were dried over MgSO4, filtered and evaporated. The product was purified by preparative SFC (Waters Viridis SFC 2-Ethylpyridine column) using an isocratic mixture of MeOH:carbondioxide (40:60). Light brown solid (0.119 g; 9%). MS (ESI): m/z=239.0 [M+H]+.

1. temperaturethe reaction mixture was heated
2. additionwas added
3. temperatureat reflux
4. customthe layers were separated
5. extractionThe aqueous layer was extracted twice with EtOAc
6. washThe organic layers were washed once with saturated aqueous NaHCO3 solution
7. extractionextracted three times with EtOAc
8. dry with materialThe organic layers were dried over MgSO4
9. filtrationfiltered
10. customevaporated
11. customThe product was purified by preparative SFC (Waters Viridis SFC 2-Ethylpyridine column)
12. additionan isocratic mixture of MeOH